Following the fertilization of sea urchin eggs, calcium is released from intracellular stores triggering the fusion of thousands of exocytotic cortical granules with the egg plasma membrane. We have used this preparation to study two aspects of calcium triggered membrane trafficking. 1) We have used light microscopy, confocal microscopy, electron microscopy, and biochemical assays to determine how eggs retrieve excess membrane following cortical granule exocytosis. We find that eggs retrieve excess membrane from the plasma membrane by directly internalizing large 1.5 microm diameter vesicles. 2) We have developed an assay using an in vitro preparation of sea urchin egg plasma membrane and cortical granules to screen drugs for their ability to lyse membranes and/or interfere with calcium triggered exocytosis. We have applied this assay to screen antineoplastic drugs to investigate the possibility that cancer might be treated by interfering with intracellular trafficking (which should be required to maintain neoplastic growth). Our assay detected two drugs which might work by this mechanism. We found that tamoxifen is membrane active and can lyse intracellular vesicles. We found that taxol acts as a reversible inhibitor of cellular secretion, and acts at a step prior to calcium activation of a fusion complex.